Project Summary: This project aims to develop a novel non-invasive technique, coherent hemodynamics spectroscopy (CHS), for the local measurement of brain perfusion and autoregulation at the microvascular level. This new technique consists of three components: (1) An experimental method based on diffuse near- infrared spectroscopy (NIRS) to non-invasively collect brain perfusion data at the microcirculation level; (2) Mild perturbations in the systemic mean arterial pressure to evoke oscillations or transients in the cerebral hemodynamics; (3) The application of a new hemodynamic model to translate NIRS measurements of cerebral hemodynamics into measurements of physiological and functional quantities. Specifically, this proposal focuses on CHS measurements of dynamic cerebral autoregulation (dCA) and capillary transit time (CTT), which yields absolute cerebral blood flow (CBF). The capability of CHS to measure local CTT, CBF, and dCA will be capitalized by developing spatially-resolved CHS (for brain mapping) and depth-resolved CHS (for discrimination of extracerebral and brain tissues). We plan clinical tests at two units at the Tufts Medical Center, namely the dialysis unit and the neurological critical care unit, to demonstrate the clinical potential of CHS. The first clinical test, on diabetic hemodialysis patients, aims to validate CHS measurements of CBF and dCA in a comparative study with age-matched healthy controls, and to demonstrate the potential of CHS to detect a reduction in cerebral perfusion during hemodialysis. The second clinical test, on patients who suffered from aneurysmal Subarachnoid Hemorrhage (aSAH) and Traumatic Brain Injury (TBI), will directly test the clinical potential of CHS in monitoring cerebral perfusion and autoregulation deficits. The broad objective of this application is the development of a new tool for the quantitative, non-invasive assessment of local cerebrovascular hemodynamics at the microcirculation level. CHS offers a significant clinical potential as a result of its ability to non-invasively assess and monitor brain tissue perfusion, which is impaired in a variety of clinical conditions, including subarachnoid hemorrhage, traumatic brain injury, hemodialysis treatment, ischemic stroke, and cardiopulmonary bypass.